Involvement of RBP4 in all‑trans retinoic acid induced cleft palate

Dong,Shiyi; Zhang,Yadong; Huang,Hongzhang

doi:10.3892/mmr.2017.7327

Involvement of RBP4 in all‑trans retinoic acid induced cleft palate

Authors:
- Shiyi Dong
- Yadong Zhang
- Hongzhang Huang
View Affiliations

Affiliations: Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‑sen University, Guangzhou, Guangdong 510055, P.R. China
Published online on: August 22, 2017 https://doi.org/10.3892/mmr.2017.7327
Pages: 5915-5923
Copyright: © Dong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The current study was designed to elucidate the mechanism of retinol binding protein 4 (RBP4) in cleft palate induced by all‑trans retinoic acid (atRA). To establish a cleft palate model in C57BL/6J mice, pregnant mice were administered atRA (100 mg/kg) by gavage at the tenth embryonic stage (E10.0). Control groups were given the equivalent volume of corn oil. Pregnant mice were dissected at E12.5, E13.5 and E14.5 to obtain the embryonic palates. The expression levels of RBP4 in the embryonic palatal mesenchyme (EPM) were determined by immunohistochemistry, reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blotting. Human embryonic palatal mesenchymal cells were exposed to atRA to detect the variation in RBP4 induced by atRA in vitro. Small interfering RNA was used to suppress the expression of RBP4, and a plasmid overexpressing RBP4 was used to examine upregulated expression. The cell counting kit‑8 assay was used to evaluate the effect of RBP4 on cell proliferation. The expression levels of p27 and cyclin D1 were determined by RT‑qPCR and western blotting, while the expression levels of extracellular signal‑related kinase (ERK) 1/2 and protein kinase B (AKT) were assessed by western blotting. At E14.5, RBP4 was strongly expressed in the EPM, while it was downregulated following atRA treatment, which induced cleft palate in vivo. In vitro experiments indicated that atRA suppressed the expression of RBP4 and altered the expression of p27 and cyclin D1 to cause growth inhibition. Knockdown of RBP4 resulted in decreased expression of cyclin D1 and increased p27, and suppressed proliferation. Overexpression of RBP4 reversed the inhibitory effect of atRA and promoted proliferation via the ERK1/2 and AKT signaling pathways. These results suggested that RBP4 was involved in cleft palate induced by atRA and it can be suppressed by atRA to cause growth inhibition in the embryonic palate.

View Figures

View References

1	Noy N: Retinoid-binding proteins: Mediators of retinoid action. Biochem J. 348:481–495. 2000. View Article : Google Scholar : PubMed/NCBI
2	Yang Q, Graham TE, Mody N, Preitner F, Peroni OD, Zabolotny JM, Kotani K, Quadro L and Kahn BB: Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature. 436:356–362. 2005. View Article : Google Scholar : PubMed/NCBI
3	Munkhtulga L, Nakayama K, Utsumi N, Yanagisawa Y, Gotoh T, Omi T, Kumada M, Erdenebulgan B, Zolzaya K, Lkhagvasuren T and Iwamoto S: Identification of a regulatory SNP in the retinol binding protein 4 gene associated with type 2 diabetes in Mongolia. Hum Genet. 120:879–888. 2007. View Article : Google Scholar : PubMed/NCBI
4	Chan TF, Tsai YC, Wu CH, Lee CH, Wang SH and Su JH: The positive correlation between cord serum retinol-binding protein 4 concentrations and fetal growth. Gynecol Obstet Invest. 72:98–1028. 2011. View Article : Google Scholar : PubMed/NCBI
5	Hatfield JT, Anderson PJ and Powell BC: Retinol-binding protein 4 is expressed in chondrocytes of developing mouse long bones: Implications for a local role in formation of the secondary ossification center. Histochem Cell Biol. 139:727–734. 2013. View Article : Google Scholar : PubMed/NCBI
6	Zhang J, Zhou S, Zhang Q, Feng S, Chen Y, Zheng H, Wang X, Zhao W, Zhang T, Zhou Y, et al: Proteomic analysis of RBP4/Vitamin A in children with cleft lip and/or palate. J Dent Res. 93:547–552. 2014. View Article : Google Scholar : PubMed/NCBI
7	Quadro L, Hamberger L, Gottesman ME, Wang F, Colantuoni V, Blaner WS and Mendelsohn CL: Pathways of vitamin A delivery to the embryo: Insights from a new tunable model of embryonic vitamin A deficiency. Endocrinology. 146:4479–4490. 2005. View Article : Google Scholar : PubMed/NCBI
8	Marazita ML and Mooney MP: Current concepts in the embryology and genetics of cleft lip and cleft palate. Clin Plast Surg. 31:125–140. 2004. View Article : Google Scholar : PubMed/NCBI
9	Wyszynski DF and Beaty TH: Phenotypic discordance in a family with monozygotic twins and nonsyndromic cleft lip and palate: Follow-up. Am J Med Genet. 110:182–183. 2002. View Article : Google Scholar : PubMed/NCBI
10	Murray JC and Schutte BC: Cleft palate: Players, pathways, and pursuits. J Clin Invest. 113:1676–1678. 2004. View Article : Google Scholar : PubMed/NCBI
11	Clagett-Dame M and DeLuca HF: The role of vitamin A in mammalian reproduction and embryonic development. Annu Rev Nutr. 22:347–381. 2002. View Article : Google Scholar : PubMed/NCBI
12	Okano J, Suzuki S and Shiota K: Involvement of apoptotic cell death and cell cycle perturbation in retinoic acid-induced cleft palate in mice. Toxicol Appl Pharmacol. 221:42–56. 2007. View Article : Google Scholar : PubMed/NCBI
13	Yu Z, Lin J, Xiao Y, Han J, Zhang X, Jia H, Tang Y and Li Y: Induction of cell-cycle arrest by all-trans retinoic acid in mouse embryonic palatal mesenchymal (MEPM) cells. Toxicol Sci. 83:349–354. 2005. View Article : Google Scholar : PubMed/NCBI
14	Mercader J, Granados N, Bonet ML and Palou A: All-trans retinoic acid decreases murine adipose retinol binding protein 4 production. Cell Physiol Biochem. 22:363–372. 2008. View Article : Google Scholar : PubMed/NCBI
15	Zhang Y, Dong S, Wang W, Wang J, Wang M, Chen M, Hou J and Huang H: Activation of Notch1 inhibits medial edge epithelium apoptosis in all-trans retinoic acid-induced cleft palate in mice. Biochem Biophys Res Commun. 477:322–328. 2016. View Article : Google Scholar : PubMed/NCBI
16	Ross SA, McCaffery PJ, Drager UC and De Luca LM: Retinoids in embryonal development. Physiol Rev. 80:1021–1054. 2000.PubMed/NCBI
17	Wang M, Huang H and Chen Y: Smad2/3 is involved in growth inhibition of mouse embryonic palate mesenchymal cells induced by all-trans retinoic acid. Birth Defects Res A Clin Mol Teratol. 85:780–790. 2009. View Article : Google Scholar : PubMed/NCBI
18	Abbott BD and Birnbaum LS: Retinoic acid-induced alterations in the expression of growth factors in embryonic mouse palatal shelves. Teratology. 42:597–610. 1990. View Article : Google Scholar : PubMed/NCBI
19	Ferguson MW: Palate development. Development. 103 Suppl:S41–S60. 1988.
20	Campbell JL Jr, Smith MA, Fisher JW and Warren DA: Dose-response for retinoic acid-induced forelimb malformations and cleft palate: A comparison of computerized image analysis and visual inspection. Birth Defects Res B Dev Reprod Toxicol. 71:289–295. 2004. View Article : Google Scholar : PubMed/NCBI
21	Rocchi M, Covone A, Romeo G, Faraonio R and Colantuoni V: Regional mapping of RBP4 to 10q23-q24 and RBP1 to 3q21-q22 in man. Somat Cell Mol Genet. 15:185–190. 1989. View Article : Google Scholar : PubMed/NCBI
22	Blaner WS: Retinol-binding protein: The serum transport protein for vitamin A. Endocr Rev. 10:308–316. 1989. View Article : Google Scholar : PubMed/NCBI
23	Wolf G: Serum retinol-binding protein: A link between obesity, insulin resistance, and type 2 diabetes. Nutr Rev. 65:251–256. 2007. View Article : Google Scholar : PubMed/NCBI
24	Vaisbuch E, Romero R, Mazaki-Tovi S, Erez O, Kim SK, Chaiworapongsa T, Gotsch F, Than NG, Dong Z, Pacora P, et al: Retinol binding protein 4-a novel association with early-onset preeclampsia. J Perinat Med. 38:129–139. 2010. View Article : Google Scholar : PubMed/NCBI
25	Singh AT, Evens AM, Anderson RJ, Beckstead JA, Sankar N, Sassano A, Bhalla S, Yang S, Platanias LC, Forte TM, et al: All trans retinoic acid nanodisks enhance retinoic acid receptor mediated apoptosis and cell cycle arrest in mantle cell lymphoma. Br J Haematol. 150:158–169. 2010.PubMed/NCBI
26	Radu M, Soprano DR and Soprano KJ: S10 phosphorylation of p27 mediates atRA induced growth arrest in ovarian carcinoma cell lines. J Cell Physiol. 217:558–568. 2008. View Article : Google Scholar : PubMed/NCBI
27	Zhang ML, Tao Y, Zhou WQ, Ma PC, Cao YP, He CD, Wei J and Li LJ: All-trans retinoic acid induces cell-cycle arrest in human cutaneous squamous carcinoma cells by inhibiting the mitogen-activated protein kinase-activated protein 1 pathway. Clin Exp Dermatol. 39:354–360. 2014. View Article : Google Scholar : PubMed/NCBI
28	Wesley UV, Hatcher JF and Dempsey RJ: Sphingomyelin synthase 1 regulates Neuro-2a cell proliferation and cell cycle progression through modulation of p27 expression and Akt signaling. Mol Neurobiol. 51:1530–1541. 2015. View Article : Google Scholar : PubMed/NCBI
29	Fillies T, Woltering M, Brandt B, Van Diest JP, Werkmeister R, Joos U and Buerger H: Cell cycle regulating proteins p21 and p27 in prognosis of oral squamous cell carcinomas. Oncol Rep. 17:355–359. 2007.PubMed/NCBI
30	Dubey RK, Fingerle J, Gillespie DG, Mi Z, Rosselli M, Imthurn B and Jackson EK: Adenosine attenuates human coronary artery smooth muscle cell proliferation by inhibiting multiple signaling pathways that converge on Cyclin D. Hypertension. 66:1207–1219. 2015.PubMed/NCBI
31	Han YH, Gao B, Huang JH, Wang Z, Guo Z, Jie Q, Yang L and Luo ZJ: Expression of CD147, PCNA, VEGF, MMPs and their clinical significance in the giant cell tumor of bones. Int J Clin Exp Pathol. 8:8446–8452. 2015.PubMed/NCBI
32	Shen H, Zhou E, Wei X, Fu Z, Niu C, Li Y, Pan B, Mathew AV, Wang X, Pennathur S, et al: High density lipoprotein promotes proliferation of adipose-derived stem cells via S1P1 receptor and Akt, ERK1/2 signal pathways. Stem Cell Res Ther. 6:952015. View Article : Google Scholar : PubMed/NCBI
33	Zhang XJ and Jia SS: Fisetin inhibits laryngeal carcinoma through regulation of AKT/NF-κB/mTOR and ERK1/2 signaling pathways. Biomed Pharmacother. 83:1164–1174. 2016. View Article : Google Scholar : PubMed/NCBI
34	Li F, Xia K, Sheikh SA, Cheng J, Li C and Yang T: Involvement of RBP4 in hyperinsulinism-induced vascular smooth muscle cell proliferation. Endocrine. 48:472–482. 2015. View Article : Google Scholar : PubMed/NCBI
35	Li F, Xia K, Sheikh MS, Cheng J, Li C and Yang T: Retinol binding protein 4 promotes hyperinsulinism-induced proliferation of rat aortic smooth muscle cells. Mol Med Rep. 9:1634–1640. 2014. View Article : Google Scholar : PubMed/NCBI
36	Takebayashi K, Sohma R, Aso Y and Inukai T: Effects of retinol binding protein-4 on vascular endothelial cells. Biochem Biophys Res Commun. 408:58–64. 2011. View Article : Google Scholar : PubMed/NCBI